Tonsilopharyngitis Diphtheriae Complicated With

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Journal of Clinical Microbiology & Infectious DiseaseJCMID. Volume 1, Number 1, January-April 2014: 6-16

Print-ISSN: 2355-1909, E-ISSN: 2355-1984.

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TONSILOPHARYNGITIS DIPHTHERIAE COMPLICATED WITHDIPHTHERITIC MYOCARDITIS IN 13 YEARS OLD GIRL AT

DR. KARIADI HOSPITAL SEMARANG-INDONESIA

1Nursyamsi-Agustina, N., 2Wahyutomo, R., 1Hapsari, MMDEAH., and 2Wahjono, H.

1Department of Pediatric, Faculty of Medicine Diponegoro University/Dr. Kariadi Hospital Semarang-Indonesia

2Department of Clinical Microbiology, Faculty of Medicine Diponegoro University/Dr. Kariadi Hospital Semarang-Indonesia

ABSTRACTBackground: Diphtheria is a frequent upper respiratory tract illness caused by Coryne-bacteriumdiphtheriaecharacterized by sore throat, low fever, malaise, anorexia and pseudo-membrane on thetonsils, pharynx, larynx and nasal cavity. Case description: It was reported that 13 years old girl

from Kudus referred to Dr. Kariadi Hospital with sore throat, low fever, hoarseness, cough,anorexia and malaise. Patient has history of immunization completely. Physical examinationindicates enlarged tonsil grade II and pseudo-membranous in the area of the tonsils, uvula, andpharynx. There was no bull neck. Results:The result of throat swab culture and Neisser stainingwere positive, Blood agar, and Telurit agar culture lead to the performance Coryne-bacteriumdiphtheriascolonies. From the result of the ECG, CK-MB and Troponin I show myocarditiss sign.Patient should be in strict isolation room until 3 times of cultures show negative results. Thetheraphy was ADS 80,000 unit i. v. (DAT treatment), penicillin procaine 50000-100000 IU/kg/dayintramuscularly for 10 days and was given prednisone for reducing inflammatory reaction that canlead to airway obstruction. Examination of serial ECG is important to look at the complications ofmyocarditis. Having obtained the results of 3 times negative cultures, and/or at least 24 hours

after completing treatment and show an improvement of symptoms, finally the patient was gettingimprovement clinically and then transferred to the inpatient ward. Conclusion: Early detectionand good blood telurit culture result is important to confirm the diagnostic of diphtheria and veryuseful for the clinicians to do the right clinical management for tonsilopharyngitis diphtheria inchildren. Subsequently, the role of clinical microbiologist in this case not only to support theclinical diagnostic but also the epidemiology in term of spreading of Corynebacterium diphtheriaeamong their family and neighbours in the community.

Keyword : Corynebacterium diphtheriae, tonsilopharyngitis diphteriae, myocarditis,

INTRODUCTION

Diphtheria is an acute, communicabledisease caused by exotoxin producingCorynebacterium diphtheriae. Review of pathologyin archived cases and the literature shows thatC.diphtheriae usually localizes in the upperrespiratory tract, ulcerates the mucosa, andinduces the formation of an inflammatorypseudomembrane.

Corresponding Author:N. Nursyamsi AgustinaDepartment of Pediatric, Faculty of Medicine

Diponegoro University/Dr. Kariadi HospitalSemarang-IndonesiaE mail: [email protected]

The exceedingly potent toxin is absorbed into

the circulation and damages remote organs,potentially resulting in death. Although primaryinfection can occur at sites other than thepharyngeal mucosa, lesions usually occur as localpseudo-membranous inflammation on mucosalsurfaces of the upper respiratory tract andsystemic lesions of the heart and (to a lesserextent) nerves.1,2

MATERIALS AND METHODSCase report

The case reported 13-year 8-month old girl

hospitalized since January 31th 2013 untilFebruary 18th 2013. Her main complaint was sorethroat (referred from Kudus Hospital with
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membranous tonsillitis suspected diphtheria).Since 4 days before hospitalization, the girlsuffered from fever, low-grade fever, no seizure,no shivering, cough (+), disphagia (-), nodischarge from ears, no nose bleeding, no gums

bleeding, no ptechie, no nausea, no vomite, nogastrointestinal and urinary tract complaints. Shewas got to physician and given some medicine.Three days before hospitalization, the girl wasstill fever, sore throat, disphagia, hoarseness, butno difficulty in breathing. The parents took her tophysician again and she was diagnosed tonsillitis.The doctor suggested to bring her to ENTspecialist. Two days later, the girl suffered fromdifficulty in speaking and sore throat increased.The parents took her to Kudus Hospital and shewas hospitalized during 1 day in ward. She

received tosmicyl injection 2x1 gr iv,metronidazol injection 3x500 mg iv, ketorolacinjection 3x1amp iv, methyl prednisolon injection2x1 amp, vitamin C injection 1x1 amp iv. In thecourse of hospitalization, the girl was dispneuthen she was referred to Kariadi Hospital. Fromphysical examination in emergency room, therewere tonsil enlargement grade II and grayishpatch pseudo-membranous in the area of thetonsils, uvula, and pharynx. There was no bullneck. The result of throat swab culture andNeisser staining were positive. Blood agar and

Telurit agar culture lead to the performanceCorynebacterium diphtherias colonies. She washospitalized in isolation room in C1L2 ward andtransferred to PINERE on January 31th 2013.Patient should be in strict isolation room until 3times of cultures showed negative results.

She lived in Islamic Education Center. Herfriends in this place suffered from sore throat andcough but there were no data about source oftransmission of diphtheria.

She was born from G2P2A0 mother, 27 yearsold, aterm. Her mother got medical check up to

midwife more than 4 times during pregnancyregularly and received vitamin, ironsupplementation, and TT injection for twice.There was no history of illness during pregnancy.Basic immunization was complete. She receivedbooster when she was in 1st class elementaryschool and no booster when she was sixth class.

Her father is a mechanic with averageincome is of IDR. 1.000.000,-/month and hermother is a housewife. Health cost was coveredby Locally State Health Insurance. Socialeconomic impression is poor. From physical

examination, a 13-year 8-month old girl, withweight was 39 kg and height was 148 cm. Generalconditions were conscious, spontaneousbreathing, and no retraction. Heart rate was 98

beats/minute and regular with good pulse.Respiratory rate was 28 times/minutes. Bodytemperature was 36,70C and blood pressure was100/65 mmHg. Head was mesocephal, eyes wereno conjunctival anemic, no icteric. Nasal flare was

negative, no nasal discharge, mouth was nocyanotic with tonsil enlargement T2-2, hyperemis,grayish pseudomembrane in tonsils, uvula, andpharynx, no lymph neck enlargement, nobullneck, tenderness (+). Chest: symmetrical, nosuprasternal and epigastrial retraction, no distantregular heart sound, and no gallop. Lungs breathsound were regular, normal and no crackles.Abdomen was flat, no enlargement of liver andspleen. All extremities were not cyanotic,capillary refill 380C),prednisone 40 mg daily (3-3-2 tablets) forreducing inflammatory reaction that can lead toairway obstruction, and diet 6x300 cc liquid diet I.Result of clinical nutrition consultation, thepatient was given diet via NGT with the need ofenergy was 1900 kcal per day, 285 gramscarbohydrates, 60 grams protein, and 58 grams

lipid.The patient was given 6x300 cc liquid diet I.On 2nd day, the patients were still dispneu, sorethroat (+). She was stridor and supraclavicularretraction on physical examination, T2-2,hyperemic, and pseudo-membrane (+). On the 3rdday, the patient was still dispneu, sore throat (+).Laboratory results were Hb 12.7 g/%, Ht 41.2%,leucocytes 27.600/mmk, erythrocyte 4.65million/mmk, thrombocyte 97.400/ mmk, MCH27.4 pg, MCV 88.6 fL, MCHC 30.9 g/dL, ureum 45mg/dL, creatinin 0.36 mg/dL, SGOT 46 U/l,

SGPT 72 U/l, CKMB 27 U/l, Troponin I


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On the 5thday, the patient was still dispneu,sore throat, and hoarseness. She looked illappearance. Pseudo-membrane was still positivein uvula, bleeding (+), but showed improvement.Tonsil was T2-2, hiperemis (+). Throat swab

culture was still positive for Corynebacteriumdiphtheria.On the 7th days, the patient was still sore

throat, dispneu, but had no fever. Generalcondition: conscious, spontaneous breathing, andill appearance. Her heart rate was 90 beats /minute and regular, good pulse, respiratory ratewas 30 times/minutes, body temperature was37,20C. Physical examination of tonsil showed T2-T2 hyperemic, pseudo-membrane was stillpositive in uvula but showed improvement.Suggestion swab and culture daily until 3 times

examination showed negative. There was noCorynebacterium diphtheriaecolonization in both ofthroat swab and culture. Prednisone began to betapering off 2-2-1 tablets (25 mg).

On the 8th days, sore throat decreased anddispneu (-). Tonsil was still T2-T2 hyperemic butpseudo-membrane (-). Second throat swab andculture showed no Corynebacterium diphtheriaecolonization. Nasogastric tube was off and tried tooral diet gradually.

On the 9th days, sore throat decreased andpatient got liquid diet II. Tonsil was still T2-T2

hiperemis but pseudo-membrane was negative.Third throat swab and culture showed noCorynebacterium diphtheriaecolonization.

On the 10th day, sore throat decreased andthe patient could eat, cough (+), dispneu (-).Tonsil was T1-1 and was not hiperemis. Procainepenicillin injection was stopped after 10 daysadministration. Ketorolac injection was stoppedand prednisone was 1-0-1 tablets (10 mg). Thepatient was transferred to C1L2 ward and thedisease gradually got improvement.

On the 12th day, sore throat was

improvement but she was still cough. There werecrackles on chest auscultation. Laboratory resultswere Hb 10.7 g/%, Ht 34.8%, leucocyte15.700/mmk, erythrocyte 3.89millions/mmk,thrombocyte 648.000/mmk, MCH 27.5 pg, MCV89.6 fl, MCHC 3.,7 g/dL, ureum 33 mg/dL,creatinine 0.91 mg/dl, SGOT 95 U/l, SGPT 256U/l, CKMB 35.6 U/l.

On 13th day, the patient complained abouthoarseness. Antibiotic have been switched toerythromycin oral 3x500 mg. She wasprogrammed to indirect laryngoscope and

consulted to pediatric cardiology. She wasassessed myocarditis diphtheria and receivedprednisone 6-5-5 tablets. On the 15th day, thepatient was still hoarseness. The result of indirect

laryngoscopy showed laryngitis. On the 16thday,laboratory result of CKMB showed 23 U/l.Electrocardiography showed sinus rhythm,normoaxis deviation, T-inverted in lead II, III, V3-V6 and depression of ST segment in lead II, V4-

V6. On the 17th day, the patient had nocomplaint. Electrocardiography showed sinusrhythm, normoaxis deviation, T inverted in leadII, III, AVF, V1-V6, and depression of ST segmentin lead II.

On the 19thday, electrocardiography showedsinus rhythm, normoaxis deviation, T inverted inlead II, III, V3-V6 and depression of ST segment inlead II. The patient got improvement and had nocomplaint. So she discharged from hospital andhad to control to policlinic.

RESULTS AND DISCUSSIONSIn this case, swab staining and culture were

positive for Corynebacterium diphtheria and thepatient was diagnosed with tonsilopharyngitisdiphtheria.

Pathology of DiphtheriaC. diphtheria is usually transmitted by direct

contact or by sneezing or coughing. Inpopulations with a high rate of immunization,improved coverage in children has shifted the age

distribution of those afflicted to unimmunized orpoorly immunized adults. Furthermore, relativelyincreased isolation of nontoxigenic strains of C.diphtheria versus toxigenic strains is noted whenimmunization rates are improved.1

Diphtheria commonly affects the tonsils,pharynx, and larynx. The C. diphtheriaremains inthe superficial mucosa or skin and elaborates itsexotoxin. The diphtheria exotoxin, a potent 62 kdpolypeptide inhibits protein synthesis leading tolocal tissue necrosis.2,4 The exotoxin is absorbedinto the mucous membranes and causes

destruction of epithelium and a superficialinflammatory response.15The necrotic epitheliumbecomes embedded in exuding fibrin and red andwhite cells, resulting in a dense necrotic coagulumof organisms, epithelial cells, fibrin, leukocytes,and erythrocytes.4,15 This advances commonlyover the tonsils, pharynx, or larynx, and becomesa gray-brown, leather-like adherent pseudo-membrane. With increase in the concentration oftoxin, it is spread to other tissues throughhaematogenous dissemination.4

Diphtheriae toxin, which is secreted by

toxigenic strains of C. diphtheriae, is a singlepolypeptide of mol weight 58,342. Toxigenicstrains of C. diphtheria carry the tox structural genefound in lysogenic corynebacteriophagesb tox1, g


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tox1, and q tox1. Highly toxic strains have two orthree tox1 genes inserted into the genome.Expression of the gene is regulated by thebacterial host and is iron dependent. In thepresence of low concentrations of iron, the gene

regulator is inhibited, resulting in increased toxinproduction. Toxin is excreted from the bacterialcell and undergoes cleavage to form two chains, Aand B, which are held together by an inter chaindisulfide bond between cysteine residues atpositions 186 and 201. As toxin concentrationsincrease, the toxic effects extend beyond the localarea due to distribution of the toxin by thecirculation.3 Diphtheria toxin does not have aspecific target organ, but myocardium andperipheral nerves are most affected.1,7,16

Human diphtheria infection may terminate

with acute cardiac failure or may prove fatalweeks later during convalescence. Examination ofheart tissues after death demonstrates cardiacdamage in many cases, although the pathologiclesions are varied and inconsistent, perhapsrepresenting a spectrum of changes related tocumulative exposure to toxin. When toxinconcentrations are low, the heart chambers maybe dilated with no effusion or malformation. Thevalves, coronary vessels, epicardium, andendocardium are normal. The myocardiumappears pale brown and soft. The myocardium

appears distorted by widely distributed areas ofgranular degeneration and loss of cross striations.Neutral fat droplets occur in 50% of fatal cases ofdiphtheria. The fat droplets appear as beadedconfigurations in the sarcoplasm of muscle cellswith oil Red O stains. Nuclei may form caterpillarchromatin configurations. Some nuclei arepyknotic. Caterpillar cells are histiocytes.Neutrophilsin the sarcoplasm of degeneratingmyocardial cells are except in areas of maximaldegeneration, where they are associated withslight hemorrhage. No other inflammatory cells

are observed. Conduction tissue lesions are notextensive. Abnormalities of coronary vessels,endocardium, or epicardium are not seen.5

Clinical PresentationClassic diphtheria is an upper-respiratory

tract illness characterized by sore throat, low-grade fever, and an adherent pseudo-membraneof the tonsil(s), pharynx, and/or nose. The diseasecan involve almost any mucous membrane.17 Thecharacteristic lesion, caused by liberation of aspecific cytotoxin, is marked by a patch or patches

of an adherent grayish-white membrane withsurrounding inflammation. The infection mostoften manifests as membranous naso-pharyngitisor obstructive laryngotracheitis.

The toxin produced by some strains cancause severe damage to the throat or other tissues.Occasionally, C. diphtheria disseminates from theskin or respiratory tract and causes invasivesystemic infections including bacteremia,

endocarditis and arthritis.18

In this case, the girl suffered from low gradefever, sore throat, cough, disphagia, hoarseness,difficult in speaking and in the course of disease,the girl was dispneu. From physical examination,there were stridor, tonsil enlargement T2-2,hyperemic, and an adherent grayish-whitepseudo-membranous in the area of the tonsils,uvula, and pharynx. These clinical manifestationswere corresponded to tonsilopharyngitisdiphtheria. This is the most common site ofinfection and is associated with the absorption of

toxin. The onset is insidious. Early symptomsinclude malaise, sore throat, anorexia and low-grade fever. Two to three days later themembrane appears in the pharyngeal/tonsillararea. The membrane initially appears white andglossy, but evolves into a dirty gray color withpatches of green or black necrosis. The extent ofthe membrane correlates with the severity ofsymptoms (i.e. with posterior pharynx, soft palateand periglottal area involvement, profoundmalaise and obstructed breathing may occur). Incases of severe disease the individual may also

develop edema of the submandibular areas andthe anterior neck, along with lymphadenopathy,giving the characteristic bullneck appearance.The individual may recover or, depending on theamount of toxin absorbed, develop severe illness,pallor, rapid pulse, stupor and coma with deathoccurring in six to 10 days.17,18 In this patient,there wasnt bullneck.

On the 13th day, the patient complainedabout hoarseness. Then she was programmed toindirect laryngoscope. The result of indirectlaryngoscope showed laryngitis.This may be

either an extension of the pharyngeal form or bethe only site involved. Symptoms include fever,hoarseness and a barking cough. Development ofthe membrane may lead to airway obstruction,coma, and death.17,18

Diagnosis of DiphtheriaDiagnosis is usually made based on history,

clinical presentation, and swab staining andculture as it is essential to begin therapy as soonas possible.Diphtheria should be suspected basedon the following clinical clues:18

mildly painful tonsillitis and/or pharyngitiswith associated membrane, especially if themembrane extends to the uvula and softpalate;


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adenopathy and cervical swelling, especiallyif associated with the membranouspharyngitis and signs of systemic toxicity;hoarseness and stridor; palatal paralysis;serosanguinous nasal discharge with

associated mucosal membrane; andtemperature elevation rarely in excess of39.4C (103F).

Figure 1Diphtheria at first presentation

Laryngeal involvement, which may occur onits own or as a result of membrane extension fromthe nasopharynx, presents as hoarseness, stridor,

croupy cough and dyspnea. These patients are atsignificant risk for suffocation because of localsoft tissue edema and airway obstruction by thediphtheritic membrane.15(level of evidence 3)

There may be toxin-mediated paralysis ofsoft palate, posterior oropharynx andhypopharynx. Although the toxin has no targetorgans the myocardium and peripheral nerves aremost affected.Other toxin mediated complicationsof diphtheria are toxic cardiomyopathy whichoccurs in 1025% of patients with respiratorydiphtheria and is responsible for 5060% of

deaths. Neurotoxicity and renal damage can alsooccur. Some of these features may present up tosix weeks after the onset of the illness suggestingan immunological basis for the pathophysiologic

mechanism for these delayed features ofdiphtheria(level of evidence 3).15

The role of the clinical microbiology in thediagnosis of diphtheria is to assist the clinicians inconfirming their clinical diagnosis. Diagnosis is

confirmed by bacteriologic examination ofspecimens. Cultures of lesions, if present and thenasopharynx are done to confirm the diagnosis.Swab(s) from the nasopharynx, especially themembrane, is essential. Isolates should be testedfor toxigenicity. Toxigenicity tests require anadditional 48 to 72 hours(level of evidence 3).15

Centre for Disease Control and Prevention(CDC 2010) defines diphtheria as:1,12

Probable: In the absence of a more likelydiagnosis, an upper respiratory tract illnesswith an adherent membrane of the nose,

pharynx, tonsils, or larynx; and absence oflaboratory confirmation; and lack ofepidemiologic linkage to a laboratoryconfirmed case of diphtheria.

Confirmed: An upper respiratory tract illnesswith an adherent membrane of the nose,pharynx, tonsils, or larynx; and any of thefollowing: isolation of Corynebacteriumdiphtheriae from the nose or throat; orhistopathologic diagnosis of diphtheria; orepidemiologic linkage to a laboratoryconfirmed case of diphtheria.

Figure 2Algorithm for laboratory diagnosis of diphtheria19

Source: Efstratiou A, Engler KH, Mazurova IK,Glushkevich T, Vuopio-Varkila J, Popovic T.

Current Approaches to the Laboratory Diagnosisof Diphtheria.


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In this case, based on history of illness, thepatient suffered from low-grade fever and cough(+) since 4 days before hospitalization . One daylater, she was sore throat, disphagia, andhoarseness. The parents take her to physician

again and she was diagnosed tonsillitis. Two dayslater, the girl suffered from difficulty in speakingand sore throat increased. The parents took her toKudus Hospital and she was hospitalized during1 day in ward. From her past history, she lived inIslamic Education Center. Her friends in her placesuffered from sore throat and cough.

From physical examination result, there weretonsil enlargement grade II and an adherentgrayish-white pseudo-membranous in the area ofthe tonsils, uvula, and pharynx. The result ofindirect laryngoscope showed laryngitis. This

may occur on its own or as a result of membraneextension from the nasopharynx. The result ofthroat swab culture and Neisser staining werepositive, Blood Telurit agar culture lead to theperformance Corynebacterium diphtherias colonies.According to CDC classification, the patient wascategorized to confirmed diphtheria because therewere upper respiratory tract illness with anadherent membrane of the nose, pharynx, tonsils,or larynx with positive culture for Corynebacteriumdiphtherias colonies(level of evidence 1).12

Figure 3

Blood agar culture of Corynebacterium diphtheria

Figure 4Blood Telurit agar culture of Corynebacterium

diphtheria

TreatmentThe treatment of diphtheria is divided into

general and specific treatment. The generaltreatments includes: 1) isolation, 2) bed rest atleast 2-3 weeks, 3) soft or liquid food dependingon the state of the patient, 4) cleanliness ofrespiratory track and liquid absorption, and 5)electrocardiography control 2-3 times a week for4-6 weeks to detect myocarditis earlier. Thespecific treatment aims to neutralize toxinproduces by diphtheria bacilli and kill diphtheriabacilli producing toxin (level of evidence 3).7

In this case, the decision to treat not onlybased on clinical manifestation but also frommicrobiology examination on the first admissionin emergency unit. Rapid detection by means ofneisser staining is important for diphtheria.

Furthermore, swab of pseudo-membranous areawere taken to confirm for diphtheriae culturestoo. The patient received general and specifictreatment. She was placed in isolation room inPINERE until having obtained the results of 3times negative cultures and took bed rest inhospital. For nutritional support, the patientreceived 6x300 cc liquid diet I via NGT with theneed of energy was 1900 kcal per day, 285 gramsof carbohydrates, 60 grams of protein, and 58grams of lipid. For specific treatment, the patientreceived procaine penicillin injection of 2 million

unit (right and left buttom) for 10 days, DAT80.000 unit, ketorolac injection 3x30 mg. Per-oral :paracetamol 4-6x500 mg (if T>38oC), prednisone40 mg daily (3-3-2 tablets) for reducinginflammatory reaction that can lead to airwayobstruction.

The most effective treatment for diphtheria isearly administration of diphtheria antitoxin(DAT), along with appropriate antimicrobialtherapy to eliminate the corynebacteria from thesite of infection thus stopping ongoing toxin-production (level of evidence 3).20 Kneen et al

showed that penicillin and erythromycin are botheffective for the treatment of diphtheria (level ofevidence 2).21

Having obtained the results of 3 timesnegative cultures, and/or at least 24 hours aftercompleting treatment and show an improvementof symptoms, finally the patient was gettingimprovement clinically and then transferred tothe inpatient ward. Finally there is no growth inculture and Neisser staining result during thefourth until sixth day hospitalization.

ComplicationToxin mediated complications of diphtheriaare toxic cardio-myopathy which occurs in 1025% of patients with respiratory diphtheria and is


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Table 1DAT treatment for cases18

Type of DiphtheriaDose

(units)Route

(one time dose*)

Nasal 10.000-20.000 IMTonsillar 15.000-25.000 IM or slow IV

Pharyngeal or laryngeal 20.000-40.000 IM or slow IV

Cutaneous 20.000-40.000 IV

Combined types or delayed diagnosis (ornasopharyngeal with membrane present)

40.000-60.000 IV

Extensive disease of > 3 days duration and/or severeswelling of neck (bullneck)

80.000-120.000 IV

*Additional doses may be warranted based on the persons symptoms and responseIM = intra muscular, IV = intra venaSource: Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines

Table 2Antibiotic treatment for case18

Age/Weight Agent Dose Duration Route

< 9 kg (20 lbs) Procaine Pen G 300.000 U BID 14 days1 IM

> 9 kg (20 lbs) Pen G 600.000 U BID 14 days1 IM

When patient can swallow comfortably:

Child2/Adult Penicillin VOR

125-250 mg QIDOR

14 days1 PO

Erythromycin 125-500 mg QID 14 days1

PO

1 Total treatment time is 14 days (i.e. if taking IM antibiotic for 10 days would complete treatment with4 additional adays of PO antibiotic

2 Use a lower Dose in children < 6 years of ageSource : Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines

Table 3Antibiotic prophylaxis for contacts and treatment for carriers of diphtheria18

Age Agent Dose Route Duration

< 6 years old Penicillin G benzathineOR

600.000 units IM One time dose

Erythromycin 40 mg/kg in 4 divided doses PO days

> 6 years old Penicillin G benzathineOR

1.2 million units IM One time dose

Erythromycin g/day in 4 divided doses PO 7-10 days

Source : Alberta Health and Wellness. Public Health Notifiable Disease Management Guidelines

responsible for 5060% of deaths. Neurotoxicityand renal damage can also occur. Some of thesefeatures may present up to six weeks after theonset of the illness suggesting an immunological

basis for the pathophysiologic mechanism forthese delayed features of diphtheria.4 Acutemortality is due to toxin-mediated diphtheriticcardio-myopathy, suffocation by the pseudo-


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membrane, disseminated intravascularcoagulation, and renal failure.The risk of cardiacinvolvement is higher in patients presenting withfever, toxic disease, and membranous disease

(level of evidence 3).22

In the course of the disease, the patientsuffered from diphtheritic myocarditis. CKMBwas 35,6 U/l. Electrocardiography showed sinusrhythm, normoaxis deviation, T inverted in leadII, III, V3-V6 and depression of ST segment in leadII, V4-V6. Then she was treated for diphtheriticmyocarditis and monitored for ECG. She was notcomplicated by both neurological and renaldisorder. Myocarditis was reported to cause highmortality.16,22,23 Clinical signs of diphtheriticcardio-myopathy become apparent by the end ofweek 2 of infection but, in severe cases, may be a

presenting feature


Diphtheritic myocarditis is frequentlycomplicated by arrhythmias that can causesudden death if not managed properly. Thepatients with cardiac involvement may beasymptomatic (ECG change and/or raised SGOT)or symptomatic (features of heart failure). TheECG changes of myocarditis may be sickle-likesagging of the ST segment (specific fordiphtheritic myocarditis), arrhythmias(supraventricular or ventricular), abnormal Qwaves, repolarization abnormalities, ST-segment

elevation > 1 mm in at least two chest leads or onelimb lead, T-wave inversion (except in leads V1and aVR), iso-electric T waves and QTc interval >0.39 s for men and > 0.41 s for women,atrioventricular block, bundle branch block,hemiblock, etc(level of evidence 3).16

Myocarditis was the most commoncomplication observed in less than 10 years of agegroup, whereas neurological complication wasmainly seen in adults. Majority of the patientswith myocarditis were asymptomatic, had onlyECG changes, SGOT elevation, and had a

favorable outcomes. Another observation wasthat almost all patients developed cardiacinvolvement within first week of onset ofrespiratory symptoms and patients who had bullneck and extensive faucial patches had moreincidence of cardiac involvement (level ofevidence 3).22

Although the presence of bull neck indiphtheria patient is associated with developmentof myocarditis according to references, but in thispatient was not like that. There was no bullneck inclinical presentation.

Kole et al reported that the most commoncomplication was myocarditis (68%), mostly wereasymptomatic (64%) and recovered with

normalization of ECG changes within 4-6 weeksof presentation. Symptomatic patients who hadmyocarditis recovered all, except one succumbedto refractory heart failure due to late presentation.Other important observations were early cardiac

involvement (within 3-4 days) and developmentof myocarditis in all patients with bull neck. Allpatient with cranial mononeuropathy recoveredwithin 6-10 weeks of presentations, but patientswith polyneuropathy required an intensive care

(level of evidence 3).24 Kneen et al reported thatclinical features at presentation provided usefulindicators of how patients will fare. Thecombination of the presence of a bull neck and apseudomembrane score of 12 was the bestpredictor that patients would develop diphtheriticcardiomyopathy, whereas the combination of

diphtheritic cardiomyopathy at hospitaladmission and a pseudomembrane score of 12was the best predictor of a fatal outcome(level ofevidence 3).25

PrognosisDiphtheria is associated with high mortality.

For those in whom the disease is recognized onthe first day and appropriate treatment institutedmortality is 1% but those in whom such treatmentis delayed till the fourth day mortality rises to20% (level of evidence 3).4

In this case, the patient had good outcomeand prognosis was good with no mortality. Itsdue to an early recognition, prompt ADSadministration, better care, and monitoring. Thepatient should be monitored closely forcomplications and checked for routine bloodbiochemistry including CPK-MB, SGOT,Troponin-T, and ECG monitoring (level ofevidence 3).24 Jayashree et al investigated theoutcome and predictors of mortality of diphtheriain children receiving intensive care. They reportedthat the immediate cause of death was

myocarditis (85%), airway compromise (11.1%)and septic shock due to nosocomial sepsis.Inadequate immunization, hypotension atadmission and presence of any complication likeairway compromise, myocarditis and renal failurehad a significant adverse effect on outcome (P


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evidence 3).23 Kole et al had been observed thatoutcomes of diphtheria were good with fewer

complications in those who were adequatelyimmunized than unimmunized patients.

Table 4Predictors for development of diphtheritic cardiomyopathy after hospital admission among 141 children

with diphtheria22

Source: Jayashree M, Shruthi N, Singhi S. Predictors of outcome in patients with diphtheria receivingintensive care. Indian Pediatr. 2006; 43: 155-60.

They reported that increase immunizationcoverage, improvement of socio-economic status,easy availability of anti-diphtheritic serum (ADS),early recognition and effective treatment mayreduce the incidence and mortality ofdiphtheria.24 (level of evidence 3).24 Vaccinatedpeople may become infected or become carriersbut have less morbidity and mortality.

In this case, the patient completed basic

immunization. She received booster when shewas in 1stclass elementary school and no boosterwhen she was sixth class. Although she wascompletely immunization, the patient stillsuffered from diphtheria. It may be caused byhaving no booster when she was sixth class. TheDT booster dose which is given at the school entryage is highly immunogenic and raises bothvaccine efficacy and antibody titer. The significantdifference in both efficacy and antibody titer inboth diphtheria and tetanus before and after thereinforcing dose emphasizes the need for such a

booster


Al Aswad reportedthat overall 87.8% of children below 12 years oldwere well immunized against diphtheria and hada protective level of diphtheria antibody ( 0.1IU/mL). There was also a significant difference ofprotection against diphtheria after the DT boosterdose given at 6 years old (P = 0.040) (level ofevidence 3).26 Ren, et al reported that maintenanceof the cold chain during transportation andstorage is needed to guarantee the effectiveness ofvaccination in remote areas. Vaccines aretemperature-sensitive biological products.

Exposure to heat shortens a vaccine's shelf life,

while freezing vaccines that should not be frozencauses irreversible loss of potency. Therefore,maintaining vaccines inside the cold chain (ICC)

is an essential part of a successful immunizationprogram (level of evidence 3).27

Figure 6Improvement of Diphtheria

CONCLUSIONEarly detection and good blood telurit

culture result is important to confirm thediagnostic of diphtheria and very useful for theclinicians to do the right clinical management fortonsilopharyngitis diphtheria in children.Subsequently, the role of clinical microbiologist inthis case not only to support the clinicaldiagnostic but also the epidemiology in term ofspreading of Corynebacterium diphtheriae amongtheir family and neighbors in the community.

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